Specific cognitive and psychological alterations are more strongly linked to increased migraine disability than chronic migraine diagnosis

Abstract

The efficiency of The International Classification of Headache Disorders (ICHD-3) in reflectingpatients’ disability has recently been questioned. This prompts consideration that clinical featuresbeyond pain may more accurately indicate the extent of underlying brain impairment than the merefrequency of headache days. Important cognitive dysfunctions and psychological impairment have beenreported in burdensome cases of migraine, and the presence of these alterations has been associated withbiological changes in the nervous system. This study aimed to compare migraine-related disabilitywithin a specific patient group, classified using ICHD-3 criteria or classified based on findings from aneuropsychological evaluation using machine learning. Additionally, a complementary voxel-basedmorphometry (VBM) comparison was conducted to explore potential neuroanatomical differencesbetween the resulting groups. Patients and methods: The study included episodic and chronic migraine patients seeking consultation at a specializedheadache department. A neuropsychological evaluation protocol, encompassing validated standardizedtests for cognition, anxiety, depression, perceived stress, and headache-related impact (HIT-6) anddisability (MIDAS), was administered. Results from this evaluation were input into an automated Kmeans clustering algorithm, with a predefined K=2 for comparative purposes. A supplementary Voxelbased Morphometry (VBM) evaluation was conducted to investigate neuroanatomical contrasts betweenthe two distinct grouping configurations. Results: The study involved 111 participants, with 49 having chronic migraine and 62 having episodic migraine.Seventy-four patients were assigned to cluster one, and 37 patients were assigned to cluster two. Clustertwo exhibited significantly higher levels of depression, anxiety, and perceived stress, and performedworse in alternating and focalized attention tests. Differences in HIT-6 and MIDAS scores betweenepisodic and chronic migraine patients did not reach statistical significance (HIT-6: 64.39 (±7,31) vs62.92 (±11,61); p= 0. 42 / MIDAS: 73.63 (±68,61) vs 84.33 (±63,62); p=0.40). In contrast, patients incluster two exhibited significantly higher HIT-6 (62.32 (±10,11) vs 66.57 (±7,21); p=0.03) and MIDAS(68.69 (±62,58) vs 97.68 (±70,31); p=0.03) scores than patients in cluster one. Furthermore, significantdifferences in grey matter volume between the two clusters were noted, particularly involving theprecuneus, while differences between chronic and episodic migraine patients did not withstandcorrection for multiple comparisons. Conclusions: The classification of migraine patients based on neuropsychological characteristics demonstrates a moreeffective separation of groups in terms of disability compared to categorizing them based on the chronicor episodic diagnosis of ICHD-3. These findings could reveal biological changes that might explaindifferences in treatment responses among apparently similar patients.